Blood cell washing systems and methods

ABSTRACT

A system and method for cleaning contaminants from shed blood to enable reinfusion of a cell concentrate in the patient employs successive rotary membrane filtering stages in which Taylor vortices are generated. Shed blood led into the first rotary membrane stage is filtered to a hematocrit in the range of 50-60 with some of the waste matter being removed. The intermediate cell concentrate is passed to the second filter stage where further waste matter is initially extracted. At any intermediate region, however, a major amount of wash solution is fed into the concentrate and effectively mixed by the Taylor vortices. In the remaining length of the second filter stage waste matter is entrained in wash solution and both waste and wash solution are filtered out to provide a cell concentrate from which the great majority of contaminants have been removed.

This is a continuation of co-pending application Ser. No. 895,505 filedon Aug. 11, 1986, now abandoned.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is related to the copending, commonly assignedapplications Ser. No. 449,470, filed Dec. 13, 1982 of Halbert Fischel,and Ser. No. 591,925 filed Mar. 21, 1984, of Donald W. Schoendorfer. Thepresent invention generally relates to method and apparatus for washingblood cells so as to permit reuse of same, such as by reinfusion to apatient's blood system.

BACKGROUND OF THE INVENTION

The first successful procedure for salvaging shed blood during anoperation or emergency situation was used more than 150 years ago, inconjunction with reinfusion of blood to hemorrhaging women subsequent tochild birth. This procedure, since termed autologous transfusion orautotransfusion, is now widely employed The return of a patient's ownblood is preferred to transfusion of blood from others because ofbiological compatibility. Autologous transfusion techniques includetaking blood from a patient prior to surgery and returning it laterduring surgery as well as temporarily removing a quantity of whole bloodand replacing it with isotonic solution. The latter procedure enablesreturn of whole blood units to the patient after major surgery, withless cell damage from pumps artificial organ devices, such as anoxygenator, for example.

A number of systems have been developed over the last 20 years for usein autotransfusion applications. Some merely collect the blood, filterfrom it relatively large particle matter such as bone fragments from atraumatic incident, and return the blood under positive pressure to thepatient. These systems are of limited applicability because they canneither concentrate the blood cells nor remove free hemoglobin,activated clotting factors or small cell debris.

Other autotransfusion machines, such as the "Cell Saver" of HaemoneticsCorporation of Braintree, Massachusetts, use centrifugation to both washand concentrate salvaged blood. This product uses a batch processingapproach and employs an expensive disposable, and therefore has limitedflexibility while being of substantial cost. However, because thewashing removes a number of constituent factors which can adverselyaffect the patient, such as liberated red cell enzymes, activatedclotting factors and anticoagulant, and because the cells areconcentrated, a higher quality blood mass is returned to the patient.Although this type of device represents the current state of the art inautotransfusion technology, its use in surgical procedures is limitedbecause a large minimum volume of packed red cells is required for thisbatch process. The same problems exist with a centrifugal unit offeredby Cobe Laboratories of Lakewood, Colorado but developed by IBM,originally for washing frozen blood but adapted by some surgical centersfor washing shed surgical blood. This unit is less expensive than theHaemonetics "Cell Saver" but much slower and more awkward to use. Bothsystems employ a saline solution for washing. A wholly differentapproach for autotransfusion, which apparently does not employ cellwashing, is disclosed in U. S. Pat. No. 4,501,581 to Kurtz et al. Inthis system primary attention is focused on deaerating the blood drawninto a collection chamber before forcing it back into the patient'scirculatory system.

It is evident, therefore, that there is a need for a system that canconcentrate blood cells, particularly for autologous transfusion, whilealso eliminating or minimizing the presence of activated substances andintracellular debris in the concentrate. The overall objectives are toreturn a high hematocrit concentrate to the patient (or to storage forlater reinfusion), while minimizing the presence of adverse factors suchas activated substances, intracellular debris, solid molecular waste andsurgical solutions (anticoagulants, salines, etc.). The system shouldmoreover be capable of functioning in a wide variety of applications,ranging from elective surgery to emergency surgery. Thus the systemshould be capable of functioning with different flow rates, volumes andcondition of blood, and should utilize low cost disposables.Specifically, any disposable should be configured to be easilyinsertable into and removable from a machine without allowingcontamination from one patient to be transmitted to another, and shouldbe so inexpensive as to introduce only a relatively low added costincrement into the procedure. It should operate on a real time, on-linebasis, with sufficient versatility of operation to meet differentconditions that may be encountered, such as a need for immediate returnof shed blood to the patient.

More recently, superior systems for plasmapheresis, or the extraction ofplasma from whole blood, have been disclosed in the above-referencedrelated patent applications of Halert Fischel entitled "BLOODFRACTIONATION SYSTEM AND METHOD", filed Dec. 13, 1982, Ser. No. 449,470,and of Donald W. Schoendorfer entitled "METHOD AND APPARATUS FORSEPARATION OF MATTER FROM SUSPENSION", filed Mar. 21, 1984, Ser. No.591,925. As described therein, blood passed into a gap between arotating spinner and a relatively fixed wall, under proper conditions ofgap size, spinner diameter and rotational velocity and flow rates cangenerate controlled and enhanced Taylor vortices within the gap.Consequently, matter, such as plasma, in the blood that is suitablysized relative to the pores of a membrane on either the spinner or theshell will pass through the membrane at rates substantially in excess ofthose heretofore achieved under similar shear and flow rate levels.Fischel describes a cell washing application where an isotonic washingsolution is passed through a porous fixed outer wall of the filter intothe gap area. Schoendorfer describes the admission of rinsing solutionsinto the gap area at or in conjunction with the point of blood admissionto the gap. Furthermore, even though the action can be continuous orintermittent, surface clogging and deposition phenomena are far lesssignificant than in planar membrane systems. Where flow throughputsdrop, moreover, the dynamic fluid conditions can be changed so as to aidin clearing the membrane as filtration continues. Systems utilizing thistechnology, such a the "Autopheresis-C" system of HemaScienceLaboratories, Inc., operate very sensitively but stably with safeguardsagainst the many factors that can affect patient comfort and safety.

SUMMARY OF THE INVENTION

Systems and methods in accordance with the invention pass shed blood insuccessive serial or concurrent parallel stages through different rotarymembrane filtration systems, at least one of which introduces a washingsolution intermediately for mixture with a concentrate. The stagesemploy Couette flow having enhanced Taylor vortices within a gap areadisposed between relatively rotating generally cylindrical surfaces atleast one of which includes a blood constituent filtering membrane. Themost used mode is a serial one, in which sufficient non-cellular andwaste matter is passed through the membrane of a first filtration unitto raise the hematocrit from its input level (e.g. 30) to the range of50-60, despite variables that can exist in the blood being processed. Aninput of substantially controlled properties, but still containing somewaste matter, is thus applied to the second filtration unit. Here theconcentrate is again filtered, but it is also mixed with a larger amountof an isotonic solution that passes through the filter membrane,carrying with it dissolved molecular material and intracellular matterso as to achieve a final hematocrit in the range of 60-70 while havingeliminated the great majority of waste material. The vorticesestablished in the gap constantly sweep the membrane surface throughoutits length, while concurrently mixing the isotonic solution with theshed blood in an extremely efficient fashion.

The same filtration units can alternatively be employed in the parallelmode, with or without substantial cell washing, in emergency and otherspecial situations.

A more specific example of a system and method in accordance with theinvention provides automatic control during different modes ofoperation. A pair of disposable units coupled serially by disposabletubing each utilize rotating spinners having covering filter membranesof less than about 1.2 micron pore size and internal passageways leadingto coaxial waste outlets. The units are contained within smallcylindrical housings that may be inserted readily into holders whichrotate the spinners. Both filter units form biologically closed systems,and pressure transducers may be used to sense the transmembranepressures therein for control purposes. Shed blood, after extraction oflarge particles in a gross filter, is stored in a cardiotomy reservoir,from which it is pumped, with or without anticoagulant depending uponthe operative procedure being used, to the first unit. Cell concentratewith some waste matter is pumped at the outlet end of the device to apooling reservoir, while the major waste flow, having passed through themembrane, flows to a bag or reservoir. The second filtration unit issomewhat like the first, but also includes an input coupled into the gapbetween the membrane covered spinner and the shell at some spacing fromthe blood input end. A saline or other wash fluid is pumped and fed intothis input at a rate approximately twice that of the partially filteredinput concentrate as it is transferred from the pooling reservoir. Wastematter and the wash fluid are mixed thoroughly and filtered through thesecond membrane, exiting into the waste bag. The vortex action withinthe device very efficiently mixes the blood concentrate with the saline,which substantially lowers the viscosity of the concentrate and entrainswaste matter within the saline flow. At the same time the vortex actionand high shear rates in the system provide a very high permeate flux ofwaste and saline through the membrane. Blood cell concentrate having ahematocrit in the 60-70 range but a very low percentage of waste matteris passed to storage for reinfusion as needed.

This system therefore provides a low cost and easily assembledconfiguration of disposables which can operate in-line and in real timewithout requiring a significant minimum amount of blood. A feature ofthe invention is that the efficiency of the filtration action in eachdevice can be monitored in terms of the transmembrane pressure, and bythe detection of hemoglobins in the waste matters. Depending upondynamic conditions, therefore, flow rates can be controlled relative toblood characteristics, and the characteristics of the cell concentratereturned to the patient can be stabilized. The filtration issufficiently through that 95% or more of all soluble elements, freehemoglobin, anticoagulant, and activated clotting factors are removedfrom the shed blood in producing the concentrated cells.

To operate the filtration units in parallel, with or without washing,only the blood and waste line couplings need be changed. This can bedone, for example, to maximize the return of blood to the patient, wheredemanded by operating conditions.

BRIEF DESCRIPTION OF THE DRAWINGS

A better understanding of the invention may be had by reference to thefollowing description, taken in conjunction with the accompanyingdrawings, in which:

FIG. 1 is a block diagram representation of an exemplary autologoustransfusion system in accordance with the invention;

FIG. 2 is a perspective view, partially broken away, of a disposablefiltering device used in the arrangement of FIG. 1;

FIG. 3 is a curve showing the relationship between concentrate flowrates and concentrate hematocrit in a typical system in accordance withFIG. 1; and

FIG. 4 is a block diagram of a modification of a portion of the systemof FIG. 1.

DETAILED DESCRIPTION OF THE INVENTION

Systems in accordance with the invention, referring now to FIGS. 1 and2, receive whole blood from a patient (during elective surgery oremergency procedures, or prior to surgery), and return concentrated redblood cells to the patient during concurrent or later surgery. Thesalvaged blood may be substantially damaged and will sometimes containlarge foreign matter, such as bone chips, metal fragments, fat globules,or extraneous tissue in emergency situations. As much as possible ofthis extraneous material is extracted in a gross filter 12 having a 10micron or larger pore size that passes all of the blood cellular matter.The blood is typically withdrawn from the patient by a pump 11 althoughin some instances gravity flow will suffice After passage through thegross filter 12, the shed blood including waste matter is temporarilystored in a cardiotomy reservoir 14, which serves as a buffer to enable,at least periodically, a continuous supply of shed blood to flow to theremainder of the system. A conventional level detector 16, which may usephotosensitive, capacitive or mass measuring techniques, providessignals to a control system 20 that controls the time and sequence ofoperation of various driving mechanisms, and the direction of flow offluids through the system. It is now common to use microprocessor-basedsystems, because of low cost and versatility, and because of ease ofuse. Many features of such a system are provided in the aforementioned"Autopheresis-C" system, but the present description, for simplicity andbrevity, will be confined to sequencing and flow control functions.

A primary mode of operation of the system is as a cell concentrator andwasher, in which a pair of Couette flow rotary filters 22, 24 are usedserially. In this mode, a blood pump 28 extracts shed blood includingwaste from the cardiotomy reservoir 14 and transfers it through a valveor diverter 30 having a single input and a pair of outputs, only one ofwhich is used in this mode. The shed blood is conducted from a firstoutput to the input 32 of the first rotary filter 22. As described inthe above-mentioned Schoendorfer application, the filter 22 includes acylindrical rotary spinner 34 that is disposed within an outer cylinder36 and covered by a filter membrane 37. The spinner 34 is rotated at agiven rate by a motor 38 via a magnetic drive coupling 40. The gapbetween the spinner 34 and the shell 36, the diameter of the spinner 34and the rotational velocity of the spinner 34 are selected, relative tothe viscosity of the input suspension, to establish high shear acrossthe membrane surface, and also to generate Taylor vortices in thesuspension, as shown somewhat idealistically in FIG. 2 for filter 24.The Taylor vortices exist in the form of helical cells extendingcircumferentially about the surface of the spinner. They have aninternal rotation within the cross section of the helices that causesthe gap fluid to constantly sweep the surface of the membrane 32. Thepore size of the membrane permits extraction of matter smaller than thepore size of the membrane (here approximately 0.8 microns although up to1.2 microns may be used in some situations) into an internal passagewaysystem (not shown) under the membrane that leads to an outlet 42 coaxialwith the spinner 34. Concentrated cellular matter in the gap between thespinner 34 and the shell 36 moves to an outlet orifice 44 for ultimatetransfer to the second rotary filter 24. As disclosed in theSchoendorfer application previously referenced, under stated conditionsthe membrane can be a stationary element positioned not on the spinner34 but on the inner wall of the shell 36, with conduits leading filtrateout from the device. Both mechanisms function with high filtratethroughput per unit area of filter and are remarkably free of depositionand concentration polarization effects. However, it is preferred toemploy the membrane on the spinner 34, inasmuch as this configuration isthe one primarily employed for plasmapheresis applications, and becauseit appears to be better suited for the wide variety of conditions thatmay be encountered in elective and emergency surgery.

Superior control is also achieved by deriving a transmembrane pressuresignal with a pressure transducer 46 coupled to the input of the firstrotary filter 22, and providing a signal to the control system 20. Theoutput side of the filter is maintained at substantially atmosphericpressure. By monitoring the transmembrane pressure in the filter 22while precisely controlling pump flow rates, an accurate reading of thestability of operation of the filter can be obtained. Internalmechanisms within the blood which may activate clotting functions, orwhich may result in incipient clogging of the membrane, can thus bedetected at an early stage and corrective measures taken.

The output 44 of the first rotary filter is coupled through a cell pump50 and a diverter valve 88 to a pooling reservoir 52 which can be usedas a buffer between the two filters 22, 24. A level detector 54 isemployed to provide signals to the control system 20 to assure that thesecond rotary filter 24 is driven only when adequate matter is availablein the reservoir 52. A cell input pump 56 transfers the onceconcentrated suspension from the pooling reservoir 52 to the input 58 ofthe second rotary filter 24. Concentrated washed cell output derived atan outlet 60 from the second filter 24 is fed, by washed cell pump 98 toa washed cell reservoir 62. Waste matter from the axial output 64 isdirected to a waste reservoir 66, along with waste taken from the axialoutput 42 of the first rotary filter 22.

The second rotary filter 24 includes a cylindrical spinner 70 that isdisposed within a cylindrical shell 72 and covered by a porous filtermembrane 73. The spinner 70 is driven by a motor 74 via a magnetic drivecoupling 76, while the filter 24 also receives, in an intermediate butcarefully chosen region along the length of the spinner 70, an injectedwash solution. Referring to FIG. 2 as well as FIG. 1, a wash fluidsource 80 provides an isotonic solution, such as a saline solution, viaa pump 82 to an injection port 84 that is coupled into the gap betweenthe spinner 70 and the shell 72 about one-third of the distance alongthe length of the spinner 70 from inlet 58 toward outlet 60. The mixingof saline with concentrate is extremely effective as the cell mass movesthrough the filter 24 because the vigorous but non-traumatic vortexaction constantly rotates matter within small cells that traverseregions adjacent the cell walls. The position of the saline input portis carefully chosen so that there is adequate additional prefiltrationof the once filtered cell concentrate input to the second rotor,adequate rotor length to provide a mix zone to mix the saline rinsesolution with the cell concentrate to in turn dilute the cells, and alsoadequate rotor length below this mix zone to finally reconcentrate thecellular matter. A position approximately 1" along a 3" long spinner isused in this specific example.

As in the first rotary filter 22, the transmembrane pressure in thesecond rotary filter 24 is sensed by a pressure transducer 86 coupled tothe input and providing an output signal to the control system 20.

A second, alternative, mode of operation, which may be used in emergencysituations or under particular conditions, should briefly be mentioned.In this mode the first and second rotary filters 22, 24 are run inparallel, each functioning as a cell concentrator in order to return redblood cells to the patient at the maximum rate. In this situation, theswitchable diverter 30, which has two output ports, is coupled to dividethe input flow from the blood pump 28 into equal flows to the inputs tothe two separate rotary filters 22, 24. A second diverter 88 coupled tothe cell pump 50 directs output flow of concentrate from the firstrotary filter 22 directly (via the dashed line flow) to the washed cellreservoir 62, along with the flow from the output 60 of the secondrotary filter 24. In severe emergency situations the cellular componentsare not washed, and the saline input is not used in order to maximizethe rate of cell reinfusion.

Referring to FIG. 3 as well as FIG. 1, the system in the most used modeof operation advantageously operates on the shed blood and waste inputby first concentrating it to hematocrit levels in the range of 50-60,eliminating a substantial quantity of blood plasma and waste materialbut providing a mass of known viscosity and controllable characteristicsto the second filter. In the second filter 24 the once concentratedblood, including waste is concentrated further. It is subjected again toenhanced vortex action with concurrent mixing of a major amount ofisotonic solution, such that both waste and the dynamically mixedwashing solution are extracted through the filter pores, leaving asuitably concentrated but thoroughly cleansed red blood cell concentratehaving a hematocrit in the range of 60-70.

The use of a separate saline input port to the filter device 24 ratherthan merely mixing saline with the concentrated blood after the firstdevice, and the optimized location of the saline input port areconsidered important design parameters which contribute significantly tothe efficiency and cost effectiveness of the system. Another significantfeature is the use of the first separator to process blood of variableconditions to a tightly controlled condition of concentration so thatthe second separator can operate efficiently. The dynamics of the systemare carried out in real time, with what may be continuous operation butwith what in most instances is a sequence of intermittent storage andprocessing steps consistent with the needs of the surgical procedurebeing undertaken.

In greater detail, the exemplary sequence proceeds as follows. Withlarge particle matter in the shed blood having been eliminated in thegross filter 12, the shed blood including waste is accumulated in thecardiotomy reservoir 14 until a suitable level is detected by thedetector 16 and control system 20. For most scheduled surgicalprocedures the blood will have been anticoagulated, as with heparin, andit will be desired to remove the anticoagulant as well as wastematerial. Whereas normal blood has a hematocrit in the range of about 37to about 50, the shed blood, with cell damage, waste matter and heparinor other additives may typically have a hematocrit as much as about 10points lower. With a predetermined minimum amount of blood detected inthe reservoir 14, the blood pump 28 begins to feed the shed blood to thefirst rotary filter 22, which process continues until the content of thereservoir 14 has reached a certain minimum. Only in rare instances wouldthe shed blood rate be greater than the input rate acceptable at thefirst rotary filter 22, and in such instances the system would typicallybe operated in parallel mode. In the typical case, however, wastematter, heparin and plasma passes through the axial outlet 42 via thepores of the filter membrane 37 on the spinner 34. At the same time,partially filtered concentrate is directed through the diverter 88 bythe cell pump 50 into the pooling reservoir 52.

As depicted in graphical form in FIG. 3, a first rotary filter 22 havinga 1" diameter and a 3" length, with a 3600 r.p.m. rate and a 0.025" gap,accepts an input flow rate of 100 ml/min and provides a concentrate flowof 30-40 ml/min and a waste and plasma output to the reservoir 66 of60-70 ml/min. The decrease in concentrate flow rate is monotonic but notlinear. The hematocrit in the concentrate correspondingly rises from itsinitial level, here about 35, to the range of 50-60, here about 55. Theconcentrate has a viscosity of 3-6 centipoises and may be pumped withoutdifficulty or the introduction of further hemolysis.

With sufficient concentrate accumulated in the pooling reservoir 52, asdetermined by signals from the level detector 54 applied to the controlsystem 20, the second rotary filter 24 may be turned on, and the cellinput pump 56 operated to provide input concentrate flow across thespinner 70 and the second rotary filter 24. At the upper end of thesecond spinner 70 there is a beneficial extraction of waste matter, thepermeate flux in this region being greater than along the comparablelength adjacent the output region of the first spinner 34. Thus there isan initial phase of removal of waste matter in the second unit, raisingthe hematocrit further and at a faster rate than the immediately priorlength in the first filter. This increase in short term permeate fluxmay be due to lower back pressure, the influence of the salineintroduced downstream, or other factors but at this time is not fullyunderstood.

Concurrently, or approximately at the time that the concentrate passesthe wash fluid injection port 84, the pump 82 to the wash fluid source80 is turned on, initiating a concurrent mixing and washing phase. Thesaline solution sharply increases the flow rate and entrains surgicalsaline, cardioplegic solution, small cell fragments and solid molecularwastes, including potentially activated materials. To a considerableextent, bacterial concentrations, such as might result from penetrationof a portion of the intestine, are also entrained in the wash solution.With about 80 ml/min of saline added, the total flow rate in the gapadjacent the saline injection port 84 is about 110 ml/min. Because ofthe intense mixing action engendered by the Taylor vortices and theconstant sweeping of matter in the vortices across the rotating filtermembrane, such materials pass rapidly through the pores in the membrane.This action is extremely effective for washing the cells. The hematocritof the concentrate moving to the outlet 60 and back to the wash cellreservoir 62 is brought up to the range of 60-70, here 65. A hematocritof 70 is the approximate maximum desirable for transfusing theconcentrate back into the patient. The waste material, anticoagulant andplasma are brought to low percentages, dependent of course on theinitial level.

It will be noted that control of the product of the first membranefiltration may be of significant importance in controlling the ultimateconcentrate, and that the interior mixing of the saline in apredetermined region (e.g. approximately one-third along the length ofthe secondary filter), together with the use of an approximately 2:1ratio of saline to the first concentrate, are also significant inachieving the desired final result in the exemplary embodiment. Thesystem is effective in eliminating 95% of all soluble elements,particularly those critical activated substances and intracellularcontents that can precipitate clotting and potential harm to therecipient.

It will be appreciated that the flow rates of the first and secondfilters are inherently unlike, inasmuch as the 100 ml/min input flowrate is reduced to an output flow of about 40 ml/min in bringing thehematocrit from the range of 30-40 to about 50 to 60 in the firstfilter. Furthermore, the addition of saline in an approximately 2:1ratio brings the total input flow rate for the second filter to amaximum of approximately 110 ml/min comprising 30-40 ml/min of partiallyconcentrated cells and 70-80 ml/min of saline. This does not mean,however, that the second filter cannot keep up with the first. To thecontrary, the filtrate flux at the second filter reaches high levelsbecause of the uniformity, low viscosity and high proportion of salineinput.

The aforementioned Schoendorfer patent application describes variouscontrol techniques for stabilizing and enhancing overall filtrationaction using transmembrane pressure as one of the gauges of operatingperformance. For example, in the event of an increase in transmembranepressure, indicative of the incipient clogging of membrane pores, flowreductions may be undertaken to dislodge surface matter by the enhancedvortex action. In the present situation, two dynamic filtration systemsare employed, and for given circumstances the rates may be adjusted tomeet particular conditions, such as to stabilize the throughput ofconcentrate for a long period of time, or to achieve high return ratesfor short periods of time.

As previously noted, however, if an emergency situation arises in whicha certain amount of cleansing action is required but the maximum rate ofreturn of red blood cell concentrate is needed, then the flow diverter30 feeds both filters 22, 24 in parallel, the wash fluid pump 82 isturned off, and concentrate outlets from both filters 22, 24 aredirected to the cell reservoir 62, which in this situation does notcontain washed cells.

Under a number of circumstances a single filtration with washing willsuffice for removal of waste matter from shed blood. This may apply, forexample, when there is a low volume of shed blood, low free hemoglobinand insubstantial amounts of anticoagulant. It is sufficient under suchconditions to direct shed blood from the cardiotomy reservoir 14 throughthe blood pump 28 and diverter 30 directly to the input 58 to the secondrotary filter 24. Using the given membrane covered spinner 70, with a 3inch length and 1 inch diameter, blood input flow rates of 40 ml/min andwash fluid rates of approximately 80 ml/min provide a suitably purifiedred cell concentrate having a hematocrit of about 60.

The example of FIG. 4 depicts how a number of other modes of operationmay be achieved in accordance with the invention. The system correspondsgenerally to that of FIG. 1, except, in part, for the incorporation ofhemoglobin detectors 92 and 96 at the first filter 22 waste output, andthe second filter 24 waste output, respectively. In addition the systemincludes a waste clamp 100 and a diverter valve 102 that is operable bythe control system to return cell concentrate to the pooling reservoir52. Both the hemoglobin detectors 92, 96 return signals indicative ofhemoglobin content to the control system 20, and all the motors arevariable speed devices (as is evident from the description of FIG. 1)that are controlled by the same system 20. Some elements and somecomponent numbers have been omitted from FIG. 4 in the interest ofbrevity and simplicity.

The system of FIG. 4 can be utilized to effect manual or automaticcontrol in a number of different modes. By sensing the hemoglobinpercentage at the waste output of the first filter 22 with thehemoglobin detector 92, for example, it can be determined whether thefree hemoglobin from the patient is within a predetermined acceptablerange. If it is, then the control system 20 operates the second filter24 in accordance with pre-established nominal conditions of flow andwash fluid input. If, however, the free hemoglobin in the waste is verylow or below a predetermined range, then the control system 20 slows thepump 82 to decrease the wash fluid input rate from the source 80,because less washing is needed. Where free hemoglobin in the waste ishigh, above the predetermined range, further washing may be needed. Forthis purpose the rate of wash fluid input can be increased. However, ifthe limit of total flow rate for satisfactory washing is reached, thediverter valve 102 is switched for a period of time, causing the washedcell output from the second filter 24 to be directed back to the poolingreservoir 52. Thereafter, when the pooling reservoir is adequately full,the cell input is recycled through the second filter 24 as wash fluidcontinues to be injected, the diverter valve 102 at this time providingthe washed cells as output. This recirculation procedure can be used aswell in other difficult situations, where an immediate washed celloutput is not required.

Furthermore, the system also has available additional control modes,based on the readings of transmembrane pressure derived at the pressuretransducers 46, 86. If the transmembrane pressure at the first filter 22increases above a given level, or rises too rapidly, filtrate flow ratescan be reduced by accelerating the cell pump 50 to prevent clogging andfacilitate clearing of the filter membrane 37.

At the second filter 24, the same expedient can be used but it can alsobe augmented by backflushing. Where filtration flow rates, establishedby the pump rates at the inputs and outputs are not commensurate withincreasing transmembrane pressure, the cell input pump 56 may be slowedand the saline flow rate increased at the pump 82. The washed cell pump98 is run at an increased rate after the filter passageways aresubstantially filled with saline, thus momentarily pulling wastematerial (mostly saline) back through the filter membrane 37,backflushing deposited material off the membrane and clearing thesystem. To further augment backflush all inputs to the second filter arearrested and waste clamp 100 of the waste output line in momentarilyclosed while the washed cell pump 95 is operated to create negativepressure which assists in the dislodgment of material such as foreignmatter or blood cells from pores of the membrane filter 37.

The portions of FIG. 1 and FIG. 4 system in contact with bloodconstituents are preferably formed of pressure disposable elements (e.g.plastic tubing, molded plastic parts assembled into connected filters,plastic reservoirs, etc.) which can be manually engaged with the activemechanical drivers, optical/pressure transducers, etc. For example, thetubing is inserted into engagement with conventional peristaltic pumps,a plastic reservoir is inserted adjacent an optical level detector, anend of the tubing may be fitted with a microbe filter and pneumaticallycoupled to a conventional pressure transducer, the plastic tubing may bepassed through an optical sensor station for sensing hemoglobin in thefiltrate, and the end of each filter may be engaged by a rotary magneticcoupled driver. A low cost, biologically closed system of low costdisposables may thus be used to implement all portions of the blood cellwashing systems which come into contact with the biological fluids.

Although the system as described is most efficacious for use in the shedblood situation where all washed cell concentrate must be returned to apatient, it will be appreciated that the system may also be utilized inother situations in which washing may be of benefit. Blood cellconcentrate stored in frozen form in an antifreeze solution may becomparably handled, using the first filter to adjust the hematocrit andthe second filter and washing stage to assure complete removal of theantifreeze carrier.

Although various alternatives and modifications have been describedabove and illustrated in the drawings, it will be appreciated that theinvention is not limited thereto but encompasses all forms andexpedients within the scope of the appended claims.

What is claimed is:
 1. A method of removing foreign matter from shedblood, comprising the steps of:passing the blood along a gap area formedbetween relatively rotating surfaces, at least one of which includes afiltering membrane; and injecting a washing solution into the gap areaonly at a predetermined localized region spaced from each end to thereentrain foreign matter in the shed blood and pass the entrained foreignmatter through the filter membrane together with the washing solutionwhile salvaging blood constituent concentrate within the gap.
 2. Themethod as set forth in claim 1 and further including the step of:firstfiltering the shed blood of some foreign matter in a first filter stageduring which no wash solution is introduced to produce an intermediatecell concentrate output, the first stage using Taylor vortices createdwithin a gap area formed between relatively rotating generallycylindrical surfaces, at least one of which includes a filteringmembrane; and next filtering the intermediate cell concentrate output ofthe first stage of additional foreign matter in a second filter stagecomprising the passing and injecting steps defined in claim 1 withwashing solution being injected, the second stage also using Taylorvortices created with the gap area to mix the washing solution andentrain the foreign matter for removal by the membrane.
 3. A method asset forth in claim 2, wherein after the first stage of filtration, theintermediate cell concentrate has a hematocrit of 50 to 60, and wherein,after the second stage of filtration, a final output cell concentratehas a hematocrit of approximately 60 to 70 and is at least about 95%free of cell debris, free hemoglobin, anticoagulant and activatedclotting factors.
 4. The method as set forth in claim 3, wherein thesecond stage of filtration comprises the steps of passing theintermediate cell concentrate along a first portion of the gap areawithout injecting washing solution to further concentrate theintermediate cell concentrate produced by the first stage, followed bymixing with a washing solution in the localized region of the gap areato dilute the intermediate cell concentrate and thereafter furtherfiltering the diluted mixture of washing solution and cell concentrate,without the injection of additional washing solution, along a thirdportion of the gap area to remove at least part of the washing solutionand entrained foreign matter.
 5. A method as set forth in claim 4,wherein the filtrates from both stages of filtering, including thefiltered washing solution, are rejected as waste, wherein the washingsolution is a saline solution, and wherein the filtering membrane haspores of 1.2 micron diameter or less.
 6. A method as set forth in claim2, further including the steps of:monitoring free hemoglobin content inthe filtrate from the first filter stage; and varying the flow rate ofinjected washing solution to the second filter stage in response to thedetected hemoglobin content to maintain the level of waste matter in thecell concentrate output within selected limits.
 7. A method as set forthin claim 6, wherein the step of injecting washing solution is varied inat least three different modes, namely: (a) nominal mode in which thewashing solution flow rate in the second stage is in a predeterminednormal range for a given normal range of free hemoglobin content inwaste filtrate from the first stage, (b) a reduced washing solution flowrate mode when the free hemoglobin content in waste filtrate from thefirst stage is below the predetermined normal range, and (c) anincreased washing solution flow rate mode in which the cell concentrateoutput from the second stage has free hemoglobin content that is abovethe predetermined normal range.
 8. A method as set forth in claim 2,further including the steps of:monitoring transmembrane filteringpressure in the first stage; and reducing blood flow through the firststage when the transmembrane pressure exceeds a predetermined limitwhile substituting a flow of washing solution and briefly interruptingthe egress of washing solution, thereby to reverse the fluid flowdirection through the filtering membrane.
 9. A method as set forth inclaim 2 further comprising the step of:recirculating at least a portionof the blood concentrate output from said second filtering stage back toits input for a second passage through the second filtering stage beforeproviding a final washed blood concentrate output.
 10. A method ofwashing shed blood constituents to derive red cell concentratecomprising the steps of:passing the blood constituents in a Couetteflow, having Taylor vortices, longitudinally along a gap area borderedby a filter membrane having a pore size of less than about 1.2 microns;feeding a wash solution capable of passing through the pores of thefilter membrane into the Taylor vortices at a rate which is at leastabout twice greater than the flow rate of the blood constituents; andfiltering foreign matter of less than about 1.2 microns size togetherwith the wash solution from the blood constituents at downstreamportions of said filter membrane.
 11. A method as set forth in claim 10,wherein the filter membrane has an active filtering length and whereinthe wash solution is injected at a predetermined intermediate zone alongthe active length and the wash solution is then mixed downstream withthe blood constituents along the filter membrane by the Taylor vortices.12. A method as set forth in claim 11 further including the stepof:initially passing the blood constituents in a Couette flow havingTaylor vortices longitudinally along a gap area bordered by an initialfiltering membrane without washing, wherein such initial filteringbrings the hematocrit of an intermediate cell concentrate to the rangeof 50 to 60 regardless of the characteristics of the input shed bloodand subsequently in said first-mentioned passing step, passing theintermediate blood concentrate alongside a second filter membrane and,in said feeding step, feeding a wash solution into the gap adjacent saidsecond filter membrane, and wherein such subsequent second filteringbrings the hematocrit of a final cell concentrate output to the range of60 to
 70. 13. A method as set forth in claim 12 including the additionalstep of recycling at least a portion of the washed cell concentrateoutput from the second filtering step while continuing to feed washsolution thereinto to filter out further waste matter, along with thefurther wash solution, from the previously washed concentrate and thusto produce a final cell concentrate output.
 14. A method as set forth inclaim 10 further including the steps of:monitoring free hemoglobinconcentration in the filtrate from at least one of the first and secondfilter stages; and varying the flow rate of the wash solution relativeto the blood flow rate in response to the monitored hemoglobinconcentration to establish a selected range of purification of thewashed cell concentration.
 15. A method as set forth in claim 10 furtherincluding the steps of monitoring transmembrane pressure and varyingflow rates to stabilize filtration efficiency in response to detectedexcessive transmembrane pressure.
 16. A method as set forth in claim 15,wherein the variation of flow rates includes the steps of:increasing theflow rate of wash fluid relative to red cell concentrate; and increasingthe back pressure against the filtrate to backflush the filter membraneso as to dislodge matter tending to clog the membrane.
 17. A method ofremoving foreign matter from a cellular suspension comprising the stepsofconveying the suspension between the inlet and outlet portions of agap formed between two surfaces, one of which includes a membranecapable of separating fluid and fluid-entrained foreign matter from thecellular component of the suspension, relatively rotating the surfacesto create vortices within the gap to sweep the suspension across themembrane, injecting a wash solution only into a localized region of thegap between its inlet and outlet portions to there entrain the foreignmatter for removal by the membrane, while retaining the cellularcomponent within the gap, and removing the cellular component from theoutlet portion of the gap.
 18. A method according to claim 17wherein thestep of injecting the wash solution includes injecting the wash solutioninto the localized area at a flow rate that is approximately twice theflow rate of the cellular suspension within the gap.
 19. A methodaccording to claim 17 or 18wherein the step of injecting the washsolution includes injecting the wash solution into the localized regionthat is located away from the inlet portion approximately one-third thedistance between the inlet and outlet portions of the gap.
 20. A methodof removing foreign matter from a cellular suspension comprising thesteps ofconveying the suspension through a gap formed between tworelatively rotating surfaces one of which includes a membrane capable ofseparating fluid from the cellular component of the suspension, forminga first concentration of cellular component within the inlet portion ofthe gap by separating fluid from the suspension without the introductionof a washing solution, further conveying the first concentration into anintermediate region of the gap away from the inlet portion where a washsolution is injected to dilute the first concentration and there entrainthe foreign matter for removal along with the fluid by the membrane,reconcentrating the diluted first concentration in the outlet portion ofthe gap by continuing to separate fluid and entrained foreign matter butwithout introducing a wash solution, and removing the reconcentratedcellular component from the outlet portion of the gap.
 21. A methodaccording to claim 20wherein the step of injecting the wash solutionincludes injecting the wash solution into the intermediate region at aflow rate that is approximately twice the flow rate of the cellularsuspension within the gap.
 22. A method according to claim 20 or21wherein the step of injecting the wash solution includes injecting thewash solution into the intermediate region that is located away from theinlet portion approximately one-third the distance between the inlet andoutlet portions of the gap.
 23. A method of removing foreign matter fromshed blood comprising the steps offirst filtering the shed blood of someforeign matter in a first filter stage during which no wash solution isintroduced to produce an intermediate cell concentrate output, nextfiltering the intermediate cell concentrate output of the first stage ofadditional foreign matter in a second stage during which washingsolution is injected to there entrain the foreign matter for removal,monitoring the free hemoglobin content in the filtrate from the firstfilter stage, and varying the flow rate of the washing solution injectedduring the second stage in response to the detected hemoglobin contentto maintain the level of foreign matter in the cell concentrate outputwithin selected levels.
 24. A method according to claim 23wherein,during the step of varying the flow rate of the washing solution;(a) thewashing solution flow rate is maintained in a predetermined normal rangewhen the detected free hemoglobin content is within a predeterminednormal range, (b) the washing solution flow rate is reduced below thepredetermined normal range when the detected free hemoglobin content isbelow the predetermined normal range, and (c) the washing solution flowrate is increased above the predetermined normal range when the detectedfree hemoglobin content is above the predetermined normal range.